Recent studies indicate that N-type and some isoforms of P/Q-type Ca2+ channels bind to presynaptic membrane proteins syntaxin and SNAP-25 and synaptic vesicle protein synaptotagmin, suggesting that presynaptic Ca2+ channels play some roles in vesicle docking, priming, and exocytosis, in addition to providing Ca2+ influx for Ca2+ dependent transmitter release. In accordance with this idea, introduction of peptides containing the synaptic protein interaction (synprint) site of N-type Ca2+ channels into terminals of cultured superior cervical ganglion neurons inhibits synchronous transmitter release. The broad objective of this proposal is to study the functional roles of Ca2+ channel-synaptic protein interactions in central synapses. Autapses of microcultred hippocampal neurons will be used for the studies. Synprint peptides will be delivered to the terminals by ionophoretic injection through whole-cell recording pipette. The types of Ca2+ channels that mediated the autaptic transmission will be identified pharmacologically. Synprint peptides of different Ca2+ channel types will be delivered to the terminals while only one type of Ca2+ channels is allowed to provide Ca2+ influx. The effects of these peptides on autaptic transmission will be monitored by single pulse, paired-pulse modulation, and post-tetanic potentiation protocols. The effects of different types of synprint peptides of Ca2+-independent transmitter release will be probed by hyperosmotic solution stimulation.